Vaccines have proven to be successful, highly acceptable methods for the prevention of infectious diseases. There are cost effective, and do not induce antibiotic resistance to the target pathogen or affect normal flora present in the host. In many cases, such as when inducing anti-viral immunity, vaccines can prevent a disease for which there are no viable curative or ameliorative treatments available.
Vaccines function by triggering the immune system to induce a response to an agent, or an antigen, typically in an infectious organism or a portion thereof that is introduced into the body in a non-infectious or non-pathogenic form.
Once the immune system has been “primed” or sensitised to the organism, later exposure of the immune system to this organism, results in a rapid and robust immune response that destroys the pathogen before it can multiply or infect enough cells in the host organism to cause disease symptoms.
The agent, or antigen, used to prime the immune system can be the entire organism in a less infectious state, known as an attenuated organism, or in some cases, component of the organism such as carbohydrate proteins or peptides representing various structural components of the organism.
In many cases, it is necessary to enhance the immune response to the antigens present in a vaccine in order to stimulate the immune system to a sufficient extent to make a vaccine effective, i.e., to confer immunity. Many proteins and most peptide and carbohydrate antigens, administered alone, do not elicit a sufficient antibody response to confer immunity. Such antigens need to be presented to the immune system in such a way that they will be recognized as foreign and will elicit an immune response.
To this end, additives like adjuvants, have been devised, which immobilise antigens and stimulate the immune response.
Recombinant proteins are promising vaccine or immunogenic composition candidates because they can be produced at high yield and purity and manipulated to maximize desirable activities and minimize undesirable ones.
However, because they can be poorly immunogenic, methods to enhance the immune response to recombinant proteins are important in the development of vaccines or immunogenic compositions. Such antigens, especially when recombinantly produced, may elicit a stronger response when administrated in conjunction with an adjuvant.
The best known adjuvant, Freund's complete adjuvant, consists of a mixture of mycobacteria in an oil/water emulsion.
Freund's adjuvant works in two ways; first, by enhancing cell and humoral-mediated immunity, and second by blocking rapid dispersal of the antigens challenge, also called “depot effect”. However, due to frequent toxic physiological and immunological reactions to this material, Freund's adjuvant cannot be used in humans.
Another molecule that has been shown to have stimulatory or adjuvant activity is endotoxin, although known as lipopolysaccharide (LPS).
LPS stimulates the immune system by triggering an immediate immune response, a response that has evolved to enable an organism to recognize endotoxin and the invading bacteria (of which it is a component) without the need for the organism to have been previously exposed. But LPS is although too toxic to be a viable adjuvant.
Thus, there is a recognized and permanent need in the art for new compounds which can be administered with antigens in order to stimulate the immune system and generate a more robust antibody response to the antigen than will be seen if the antigens were injected alone.
Additionally, it should be noted that parenteral administration i.e. intramuscularly or sub-cutaneous, of antigens of vaccines are normally regarded as the most convenient way of administration.
However, the injection presents a range of disadvantages. It requires the use of sterile syringes and may cause pains and irritations, particularly in the case of repeated injections, including the risk of infection. More significantly, intramuscularly injections are often poorly tolerated. There is often likely to be indurations (hardening of tissue) haemorrhages and/or necrosis (local death of tissue) at the injection site. Besides, untrained person cannot administer injections.
Based on these observations, it should be noted that mucosal immunity has take a considerable importance in vaccine development because nearly all viral, bacterial and parasitic agent that cause disease of the intestinal, respiratory and genital tracks enter through the mucosal barrier. Furthermore, mucosal and systemic immune responses are often elicited and regulated independently, and induction of protective immunity at the most frequent sites of entry is likely to be most effective. Additionally, young children and elderly individuals may respond better to mucosal vaccines because the mucosal immune system develops earlier and appears to remain functional longer than the systemic compartment. Mucosal immunisations are also easier and less expensive than systemic immunisations. For example, the existence of an oral polio vaccine has allowed immunisation campaigns that may soon eradicate polio worldwide.
Accordingly, it is also an object of the present invention to provide a vaccine composition comprising an immunoadjuvant compound which could be administered by the mucosal route. These and further objects will be apparent to one ordinary skill in the art.